Role of MyD88-dependent and MyD88-independent signaling in Porphyromonas gingivalis-elicited macrophage foam cell formation.

Role of MyD88-dependent and MyD88-independent signaling in Porphyromonas gingivalis-elicited macrophage foam cell formation.
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MyD88 依赖性和 MyD88 独立信号在牙龈卟啉单胞菌引起的巨噬细胞泡沫细胞形成中的作用。

DOI:
10.1111/omi.12003
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发表时间:
2013
影响因子:
3.7
通讯作者:
Gibson3rd,FC
Gibson3rd,FC
中科院分区:
医学3区
文献类型:
--
作者:
Shaik-Dasthagirisaheb,YB;Huang,N;Baer,MT;Gibson3rd,FC

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临床研究和实验模型确定了牙周病和牙周病原体如牙龈卟啉单胞菌和动脉粥样硬化和巨噬细胞泡沫细胞形成之间的潜在联系。Toll样受体和控制其细胞内信号通路的分子(如MyD 88)在动脉粥样硬化以及宿主对牙龈卟啉单胞菌的反应中发挥作用。本研究的目的是明确MyD 88和TRIF在牙龈卟啉单胞菌诱导的巨噬细胞泡沫细胞形成过程中的作用。在存在人低密度脂蛋白(LDL)的情况下,与牙龈卟啉单胞菌一起培养的小鼠骨髓源性巨噬细胞(BMφ)的肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)显著降低。无论细菌攻击是否与LDL处理同时发生或在LDL处理之前发生,BMφ均被油红O强烈染色。热灭活的牙龈卟啉单胞菌以与活细菌相似的方式刺激泡沫细胞形成。MyD 88敲除和Lps 2小鼠的BMφ显示MyD 88在牙龈卟啉单胞菌诱导的泡沫细胞形成中具有显著作用,TRIF在牙龈卟啉单胞菌诱导的泡沫细胞形成中具有次要作用。牙龈卟啉单胞菌诱导的TNF-α和IL-6受MyD 88消融的影响,受TRIF状态的影响程度较小。这些数据表明,LDL影响巨噬细胞对牙龈卟啉单胞菌攻击的TNF-α和IL-6反应,MyD 88和TRIF在牙龈卟啉单胞菌诱导的泡沫细胞形成中起重要作用。
Clinical studies and experimental modeling identify a potential link between periodontal disease and periodontal pathogens such asPorphyromonas gingivalisand atherosclerosis and formation of macrophage foam cells. Toll‐like receptors and molecules governing their intracellular signaling pathways such as MyD88 play roles in atherosclerosis, as well as host response toP. gingivalis. The aim of this study was to define roles of MyD88 and TRIF during macrophage foam cell formation in response toP. gingivalis. In the presence of human low‐density lipoprotein (LDL) mouse bone‐marrow‐derived macrophages (BMφ) cultured withP. gingivalisresponded with significant reduction in tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). The BMφ stained strongly with oil red O, regardless of whether bacterial challenge occurred concurrent with or before LDL treatment. Heat‐killedP. gingivalisstimulated foam cell formation in a similar way to live bacteria. The BMφ from MyD88‐knockout and Lps2 mice revealed a significant role for MyD88, and a minor role for TRIF inP. gingivalis‐elicited foam cell formation.Porphyromonas gingivalis‐elicited TNF‐α and IL‐6 were affected by MyD88 ablation and to a lesser extent by TRIF status. These data indicate that LDL affects the TNF‐α and IL‐6 response of macrophages toP. gingivalischallenge and that MyD88 and TRIF play important roles inP. gingivalis‐elicited foam cell formation.
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